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Mir-150上调骨肉瘤细胞中的Glut1并增加糖酵解

Mir-150 Up-Regulates Glut1 and Increases Glycolysis in Osteosarcoma Cells.

作者信息

Yuan Guangke, Zhao Yanqing, Wu Dongjin, Gao Chunzheng

机构信息

Department of Orthopedics, The Second Hospital of Shandong University, Shandong University, China. Email:

出版信息

Asian Pac J Cancer Prev. 2017 Apr 1;18(4):1127-1131. doi: 10.22034/APJCP.2017.18.4.1127.

Abstract

Objective: Osteosarcoma (OS) is the most common malignant bone tumor in children and young adults. Many studies have shown that microRNAs play a critical role in proliferation and metastasis with this tumour type. However, whether aberrant expression might contribute to a metabolism switch in osteosarcoma cases is not clearly understood. In this study, we explored expression and function of miR-150 in osteosarcoma cells. Materials and methods: Expression of miR-150 was assessed by real-time PCR in cell lines and human patient tissues. Scramble siRNA, miR-150 inhibitor, and miR-150 mimics were transfected into osteosarcoma cells to determine their effects on proliferation rate, glucose uptake and lactate secretion. Finally, the relationship between Glut1 and the miR-150 level was explored by luciferase reporter assay and western blotting. Result: miR-150 was consistently decreased in cell lines and osteosarcoma tissues as compared to osteoblast cells and normal bone. Ectopic overexpression of miR-150 inhibited osteosarcoma cell proliferation and suppressed glucose uptake and lactate secretion. Loss of function of miR-150, on the other hand, enhanced osteosarcoma cell proliferation and increased glucose uptake and lactate secretion. Western blot and luciferase reporter assays showed that miR-150 may function by regulating Glut1 expression. Conclusion: These data suggest that miR-150 is involved in regulation of glycolysis in osteosarcoma cells by influencing Glut1 expression.

摘要

目的

骨肉瘤(OS)是儿童和青年中最常见的恶性骨肿瘤。许多研究表明,微小RNA在这种肿瘤类型的增殖和转移中起关键作用。然而,异常表达是否可能导致骨肉瘤病例中的代谢转换尚不清楚。在本研究中,我们探讨了miR-150在骨肉瘤细胞中的表达和功能。材料和方法:通过实时PCR评估细胞系和人类患者组织中miR-150的表达。将乱序siRNA、miR-150抑制剂和miR-150模拟物转染到骨肉瘤细胞中,以确定它们对增殖率、葡萄糖摄取和乳酸分泌的影响。最后,通过荧光素酶报告基因测定和蛋白质印迹法探讨Glut1与miR-150水平之间的关系。结果:与成骨细胞和正常骨相比,细胞系和骨肉瘤组织中miR-150持续降低。miR-150的异位过表达抑制了骨肉瘤细胞的增殖,并抑制了葡萄糖摄取和乳酸分泌。另一方面,miR-150功能丧失增强了骨肉瘤细胞的增殖,并增加了葡萄糖摄取和乳酸分泌。蛋白质印迹和荧光素酶报告基因测定表明,miR-150可能通过调节Glut1表达发挥作用。结论:这些数据表明,miR-150通过影响Glut1表达参与骨肉瘤细胞糖酵解的调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fff/5494226/219f0bdcc0fc/APJCP-18-1127-g001.jpg

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